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Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV

2005; Elsevier BV; Volume: 107; Issue: 3 Linguagem: Inglês

10.1182/blood-2005-04-1492

1528-0020

Maria Grazia Narducci, Enrico Scala, Antonella Bresin, Elisabetta Caprini, Maria Cristina Picchio, Daniele Remotti, Gianluca Ragone, Francesca Nasorri, Marina Frontani, Diego Arcelli, Stefano Volinia, Giuseppe Lombardo, Giannandrea Baliva, Monica Napolitano, Giandomenico Russo,

Cutaneous lymphoproliferative disorders research

Abstract Sézary syndrome (SS) is a rare form of cutaneous T-cell lymphoma (CTCL) characterized by a distinct metastatic pattern mainly involving blood and skin. Chemokines and their receptors play a critical role in cellular recruitment and homing to tissues and in the metastatic process of several tumors including non-Hodgkin T-cell lymphomas (NHLs). Here we report that SS cells express a functionally active CXCR4 and that its ligand SDF-1 is abundantly produced in the skin, which represents the main destination of SS cell spreading. SDF-1 is normally inactivated by proteolytic cleavage by the CD26/dipeptidylpeptidase IV (DPPIV). The lack of CD26 from the cell surface is a hallmark of circulating SS cells. We also show that the CD26- phenotype is maintained also in skin-infiltrating neoplastic T lymphocytes and that SS-affected individuals exhibit a reduced activity of plasma soluble CD26. Finally, we observe that the addition of soluble CD26 reduces the migratory response of SS cells to SDF-1 whereas the inhibition of the CD26 peptidase activity in Hut78, a CD26+ CTCL cell line, enhances the SDF-1-induced migration of these cells. Our findings suggest that the SDF-1-CXCR4 axis could play an important role in skin homing of SS through the regulatory activity of CD26.